Acral lentiginous melanoma in Hawaii: Characterization of the mTOR pathway in the non-Caucasian population.

Abstract

8592 Background: Although, acral lentiginous melanoma (ALM) is the least common subtype among patients with melanoma, there is a higher preponderance in the non-Caucasian population. ALM has been proposed to have a different pathogenesis. Recent studies have profiled the importance of the mTOR (mammalian target of rapamycin) pathway in carcinogenesis. However, characterization of this pathway in a multi-ethnic ALM population has not been reported. The Pacific Basin provides a unique opportunity to study diseases in non-Caucasian patients. We elected to determine the frequency of mTOR pathway involvement in ALM. Methods: IRB approval was obtained for this retrospective analysis. From 1992 to 2010, 20 non-Caucasian patients (9-Filipino, 4-Micronesian, 4-Samoan, 1-Thai, 1-unspecified Pacific Islander and 1-Vietnamese) histologically confirmed to have ALM were evaluated at a tertiary institution. Data including age, gender, tumor location, Breslow thickness, Clark level, ulceration, regression, and mitoses per mm squared were compiled. Immunohistochemical expression for mTOR and eIF4E (eukaryotic initiation factor 4E) proteins was performed on formalin-fixed/ paraffin-embedded archived biospecimens (primary lesions). Both m-TOR and eIF4e expression were graded on a scale from 0 (absent) to 2 (high). Results: Our results demonstrated that the mTOR protein 14/20 (70%) and eIF4E protein 9/20 (45%) were highly expressed. Demographics of the non-Caucasian cohort include mean age of 69.6 years old (range 48-89) and male gender 10/20 (50%). Tumor location principally involved the foot 19/20 (95%); mean Breslow thickness was 4.36 mm (range 1.6-10.0), Clark IV or higher 16/20 (80%), ulceration 16/20 (80%), regression 20/20 (100%), and mean mitoses per mm squared was 8.5 (range 1-30). Conclusions: Non-Caucasian patients with ALM were found to have a high prevalence of effectors involving the mTOR pathway. Nearly half of our cohort had thick primary lesions with a high propensity for ulceration. This is the first study to our knowledge that has examined the mTOR pathway in a non-Caucasian population of ALM patients. This is compelling data that may be applied to the metastatic phenotype in future trials.